公开(公告)号：US07238814B2

公开(公告)日：2007-07-03

申请号：US10781705

申请日：2004-02-20

Applicant: Przemyslaw A. Marek ,  Andzrej M. Trocha ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson

Inventor： Przemyslaw A. Marek ,  Andzrej M. Trocha ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson

IPC: C07D209/56 ,  C07D263/00 ,  A61K31/395 ,  A61K31/421

CPC classification number: A61B5/4368 ,  A61B5/015 ,  A61K49/0004 ,  Y10S514/929

Abstract: The invention describes compositions and kits comprising 4-aza-4-(2-methyl-2-sulfanylpropyl) tricyclo(5.2.1.0 )dec-8-ene-3,5-dione; 4-aza-4-(2-methyl-2-(nitrosothio)propyl) tricyclo(5.2.1.0 )dec-8-ene-3,5-dione; 4-{1-methyl-1-((2,4,6-trimethoxyphenyl)methylthio)ethyl}-1,3-oxazolidin-2-one; 2-aAmino-3-methyl-3-((2,4,6-trimethoxyphenyl)methylthio)butan-1-ol; 4-(1-methyl-1-(nitrosothio)ethyl)-1,3-oxazolidin-2-one; or pharmaceutically acceptable salts thereof. The compositions of the invention can further comprise at least one penetration enhancer, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent.

Abstract translation: 本发明描述了包含4-氮杂-4-（2-甲基-2-硫烷基丙基）三环（5.2.1.0 2,6）癸-8-烯-3,5-二酮的组合物和试剂盒; 4-氮杂-4-（2-甲基-2-（亚硝基硫基）丙基）三环（5.2.1.0 2,6）癸-8-烯-3,5-二酮; 4- {1-甲基-1 - （（2,4,6-三甲氧基苯基）甲硫基）乙基} -1,3-恶唑烷-2-酮; 2-（2-氨基-3-甲基-3 - （（2,4,6-三甲氧基苯基）甲硫基）丁-1-醇; 4-（1-甲基-1-（亚硝基硫代）乙基）-1,3-恶唑烷-2-酮; 或其药学上可接受的盐。 本发明的组合物可进一步包含至少一种渗透增强剂，至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物 合成酶和/或至少一种血管活性剂。

公开(公告)号：US06762202B2

公开(公告)日：2004-07-13

申请号：US09850081

申请日：2001-05-08

Applicant: Przemyslaw A. Marek ,  Andzrej M. Trocha ,  Chia-En Lin ,  Ramani R. Ranatunga ,  Stewart K. Richardson

Inventor： Przemyslaw A. Marek ,  Andzrej M. Trocha ,  Chia-En Lin ,  Ramani R. Ranatunga ,  Stewart K. Richardson

IPC: A01N4740

CPC classification number: A61B5/4368 ,  A61B5/015 ,  A61K49/0004 ,  Y10S514/929

Abstract: The present invention describes rapid noninvasive methods for measuring vasodilation or changes in blood flow in a patient following administration of at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The method comprises the administration of at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent to the patient followed by monitoring the temperature change of an area of interest using infrared thermography. The present invention provides methods for diagnosing diseases or disorders related to vasodilation and changes in blood flow, such as, sexual dysfunction, Raynaud's syndrome, inflammation, hypertension, gastrointestinal disorders and central nervous system disorders. The sexual dysfunction is preferably female sexual dysfunction and female sexual arousal. The vasoactive agents include potassium channel activators, calcium channel blockers, &agr;-adrenergic receptor antagonists, &bgr;-blockers, phosphodiesterase inhibitors, adenosine, ergot alkaloids, vasoactive intestinal peptides, prostaglandins, dopamine agonists, opioid antagonists, endothelin antagonists and thromboxane inhibitors. The present invention can also be used to screen and identify drug candidates for treating diseases, disorders and conditions resulting from vasodilation or changes in blood flow. The present invention also describes compositions comprising at least one S-nitrosothiol compound for diagnosing, monitoring and/or treating female sexual dysfunctions.

Abstract translation: 本发明描述了在给予至少一种捐赠，转移或释放一氧化氮的化合物，升高内源性内皮衍生的松弛因子水平，刺激一氧化氮的内源性合成之后测量患者血管舒张或血流变化的快速非侵入性方法 或者是用于一氧化氮合酶和/或至少一种血管活性剂的底物。 该方法包括施用至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮衍生的松弛因子水平，刺激一氧化氮的内源性合成，或者是一氧化氮合酶和/或至少一种血管活性物质的底物 然后使用红外热像仪监测感兴趣区域的温度变化。 本发明提供了用于诊断与血管舒张和血流变化有关的疾病或病症的方法，例如性功能障碍，雷诺综合征，炎症，高血压，胃肠道疾病和中枢神经系统疾病。 性功能障碍最好是女性性功能障碍和女性性唤起。 血管活性剂包括钾通道激活剂，钙通道阻滞剂，α-肾上腺素能受体拮抗剂，β-阻断剂，磷酸二酯酶抑制剂，腺苷，麦角生物碱，血管活性肠肽，前列腺素，多巴胺激动剂，阿片样物质拮抗剂，内皮素拮抗剂和血栓烷抑制剂。 本发明还可用于筛选和鉴定用于治疗由血管舒张或血流变化引起的疾病，病症和病症的候选药物。 本发明还描述了包含至少一种S-亚硝基硫醇化合物用于诊断，监测和/或治疗女性性功能障碍的组合物。